The long term goal of the proposed research is to understand the control of eukaryotic cell proliveration by studying the molecular mechanisms involved in the replication of the genomes of the human adenoviruses. Adenovirus DNA replication will be studied using a soluble in vitro system capable of replicating exogenously added viral DNA. Virus- and cell-coded replication proteins involved both in the initiation of replication and the elongation of DNA chains will be purified and characterized. In addition, viral DNA sequences important in the initiation of replication will be identified by studying the replication of mutant DNA templates constructed in vitro using recombinant DNA techniques.